Last year, CRISPR-Cas9 stole international headlines as scientists across the globe debated whether or not the revolutionary gene-editing technology should be used to modify DNA in human embryonic cells. CRISPR works by targeting and making incisions at a specific DNA sequence, enabling scientists to mute genes or to replace them altogether.
Yet the implications of manipulating DNA with such ease are twofold: on one hand, CRISPR may provide scientists with the opportunity to edit pernicious diseases out of our DNA. On the other, germ-line editing may make irreversible and heritable modifications within the human genome, heralding an era of ethically ambiguous and potentially damaging research.
“A lot of the controversy is centered on figuring out what the permissible uses of this technology will be,” Elliot Hosman, Senior Program Associate at the Center for Genetics and Society, tells BTRtoday.
Among those who wish to implement CRISPR to combat disease is Kamel Khalili, Ph.D, senior investigator on a new study to emerge from the Lewis Katz School of Medicine at Temple University.
Khalili and his team used the gene-editing software to target HIV, and they succeeded in removing the disease’s genome from infected cells without causing damage to those cells. Their findings were published in this month’s issue of Scientific Reports.
When a person becomes infected with HIV, the virus attacks an important class of white blood cells called CD4 T-cells and integrates its genome into their DNA. As the cells continue to reproduce, they generate more and more of the HIV’s genome, allowing it to further weaken the person’s immune defenses.
“Antiretroviral drugs are very good at controlling HIV infection,” Khalili said. “But patients on antiretroviral therapy who stop taking the drugs suffer a rapid rebound in HIV replication.”
Khalili and his team used CRISPR to specifically target HIV-1 proviral DNA (DNA carrying the HIV genome). Once the virus’s genome was snipped out of the infected strands of DNA, the loose ends were reunited naturally, causing no harm to the host cell.
“The findings are important on multiple levels,” Khalili explained. “They demonstrate the effectiveness of our gene editing system in eliminating HIV from the DNA of CD4 T-cells and, by introducing mutations into the viral genome, permanently inactivating its replication. Further, they show that the system can protect cells from reinfection and that the technology is safe for the cells, with no toxic effects.”
As a new technology, CRISPR still has many bugs that need to be addressed.
Hosman explains that in some cases, once CRISPR has been injected into a cell, it will continue to make incisions not only at the target sequence but also at similar sequences, ad infinitum.
That Khalili’s team was able to protect the integrity of the cells in which CRISPR removed the virus’s genome is monumental. He notes that while similar studies have previously been conducted, none have performed to this extent.
“But the questions they address are critical,” he said, “and the results allow us to move ahead with this technology.”